English bulldogs are an animal model for sleep-disordered breathing (SDB). In these dogs, SDB occurs much more frequently in REM than in non-REM sleep. This laboratory has recently shown that SDB was associated with normal phasic REM sleep-related changes in respiratory muscles: fractionations, asynchrony, and intermittent decrements in drive. Furthermore, respiratory drive to an upper airway dilating muscle during non-REM, when SDB is absent in bulldogs, was increased compared to drive in normal dogs (beagles). It thus appears that airway collapse in waking and non-REM sleep is prevented only by increased neural drive to upper airway dilators. We propose that this increase in neural activity is a response to the anatomic narrowing of the upper airways. The protocols in this proposal aim to establish the mechanisms and consequences of this long-term, near-continuous hyperactivity of upper airway dilating muscles. A group of protocols (A) will investigate the physiology, pharmacology (especially serotonin), and dynamic anatomy (as measured by cine CT imaging) of the upper airway and its dilator muscles in unanesthetized, unrestrained, chronically instrumented bulldogs and control dogs. In addition, the planned studies will establish whether the chronic increased activity has permanent consequences, specifically use-dependent neural plasticity (Protocol B) and changes in muscle morphology and function (Protocol C). This will be accomplished by comparing dogs with chronic tracheostomies to those breathing through their natural upper airways. This work will be conducted using sophisticated techniques for dynamic imaging, neuroanatomy, and muscle biology, in addition to sleep studies and chronic recording from unrestrained, unanesthetized animal preparations. It represents a novel and integrated approach to some of the most basic questions in the field: neuromuscular adaptations to chronic obstruction and possible mechanisms underlying the eventual failure of these adaptive responses.